title: Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells.
abstract: OBJECTIVE
  We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs).
  
  
  METHODS
  The production of CEA was investigated in LoVo cells that were cultured with 0-10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.
  
  
  RESULTS
  Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells.
  
  
  CONCLUSIONS
  Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments.
authors.affiliation: Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan.
authors.forename: Hsin-chung
authors.initials: HC
authors.lastname: Lee
authors.forename: Qing-Dong
authors.initials: QD
authors.lastname: Ling
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Yu
authors.forename: Chunh-Ming
authors.initials: CM
authors.lastname: Hung
authors.forename: Ta-Chun
authors.initials: TC
authors.lastname: Kao
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Huang
authors.forename: Akon
authors.initials: A
authors.lastname: Higuchi
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010455:Peptides / Q000032:analysis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse
keywords: 5-fluorouracil; CD133; colon cancer cell; drug treatment; stem cell